Position 120-123, a potential active site of trichosanthin.
Trichosanthin (TCS) is a type-I ribosome-inactivating protein (RIP) with wide spectrum of biological and pharmacological activities. In the present study, a potential site on the TCS molecule (position 120-123) is identified which may be important for the biological activities of TCS. By using site-directed mutagenesis, position 120-123 of TCS was either deleted or changed from Lys-Ile-Arg-Glu (hydrophilic) to Ser-Ala-Gly-Gly (hydrophobic). Deletion of these residues rendered a TCS molecule completely deprived of ribosome inactivating activity, while hydrophobic replacement caused 4000-fold decrease in ribosome inactivating activity. The abortifacient activity of these two mutants was retained with decreased potency. This implies that position 120-123 of the native TCS molecule plays a critical role in maintaining its biological activity.
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Shanghai Institute of Cell Biology, Academia Sinica, China.
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D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007124:Immunoenzyme Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D016297:Mutagenesis, Site-Directed; D011817:Rabbits; D012270:Ribosomes / Q000187:drug effects; D013329:Structure-Activity Relationship; D015978:Trichosanthin / Q000737:chemistry / Q000494:pharmacology*
D000020:Abortifacient Agents, Nonsteroidal; D015978:Trichosanthin